Potential Applications of Blautia wexlerae in the Regulation of Host Metabolism.

Blautia wexlerae (B. wexlerae) is a strong candidate with the potential to become a next-generation probiotics (NGPs) and has recently been shown for the first time to exhibit potential in modulating host metabolic levels and alleviating metabolic diseases. However, the factors affecting the change in abundance of B. wexlerae and the pattern of its abundance change in the associated indications remain to be further investigated. Here, we summarize information from published studies related to B. wexlerae; analyze the effects of food source factors such as prebiotics, probiotics, low protein foods, polyphenols, vitamins, and other factors on the abundance of B. wexlerae; and explore the patterns of changes in the abundance of B. wexlerae in metabolic diseases, neurological diseases, and other diseases. At the same time, the development potential of B. wexlerae was evaluated in the direction of functional foods and special medical foods.

What is a "Distinctive Nutritional Requirement"? A Position Paper of the Healthcare Nutrition Council.

The Healthcare Nutrition Council (HNC) represents manufacturers of enteral nutrition formulas and oral nutrition supplements, including those categorized as medical foods and parenteral nutrition. HNC member companies, Abbott's Nutrition Division, Nestlé Health Science, and Nutricia North America, a subsidiary of Danone S.A., manufacture a majority of the medical foods consumed in the United States. HNC is proposing a modernized interpretation of the medical food framework to reflect the evolution of nutrition science and health care. The medical food category was first defined in 1988 as part of the Orphan Drug Act. Since then, the scientific community's understanding of nutrition and the role it can play in disease management has progressed. HNC believes that a patient-centric approach is needed to foster research and innovation and to position medical foods as a viable solution in the dietary management of disease. HNC proposes that distinctive nutritional requirements refer to the clinical need for a specific nutritional intake (compared with the intake of healthy populations), which may exist by reason of abnormal physiologic manifestation or physical impairment associated with a disease or condition. The dietary management of these diseases and conditions results in clinically meaningful improvements, including but not limited to nutritional status, health outcomes, or quality of life. HNC believes that abnormal physiologic manifestation or physical impairment would include a limited, impaired, or disturbed capacity to ingest, digest, absorb, metabolize, or excrete ordinary food or certain nutrients or metabolites or other medically determined requirements for nutrients or other food substances of biological value. HNC recommends our position be considered as we build consensus across the industry. We request that the Food and Drug Administration modify and codify the current definition to reflect this. Patients and the health care system will benefit from a strong regulatory interpretation of the medical foods framework.

Role and Importance of Functional Food Packaging in Specialized Products for Vulnerable Populations: Implications for Innovation and Policy Development for Sustainability.

Specialized products can be needed to help meet the nutrition requirements of vulnerable populations, including infants and young children, those who are ill, and older adults. Laws and regulations delineate distinct categories for such products including medical foods or formulated liquid diets, foods for special dietary use (FSDUs), infant formulas, and natural health products (NHPs). Yet, the literature is limited regarding the role and importance of functional and sustainable packaging for specialized products. This perspective review describes these unique product categories and the role of packaging as well as regulatory considerations. Furthermore, reviewed are how waste reduction strategies and emerging legislative/regulatory policies in the United States and Canada may not adequately address the functional packaging requirements for specialized products. The paper concludes by offering perspectives for emerging innovations and policy development for sustainability.

Nutraceuticals with Anti-inflammatory and Anti-oxidant Properties as an Intervention for Reducing the Health Effects of Fine Particulate Matter: Potential and Prospects.

Air pollution, especially particulate matter pollution, adversely affects human health. A growing pool of evidence has emerged which underscores the potential of individual-level nutritional interventions in attenuating the adverse health impact of exposure to PM2.5. Although controlling emission and reducing the overall levels of air pollution remains the ultimate objective globally, the sustainable achievement of such a target and thus consequent protection of human health will require a substantial amount of time and concerted efforts worldwide. In the meantime, smaller-scale individual-level interventions that can counter the inflammatory or oxidative stress effects triggered by exposure to particulate matter may be utilized to ameliorate the health effects of PM2.5 pollution. One such intervention is the incorporation of nutraceuticals in the diet. Here, we present a review of the evidence generated from various in vitro, in vivo and human studies regarding the effects of different anti-inflammatory and antioxidant nutraceuticals in ameliorating the health effects of particulate matter air pollution. The studies discussed in this review suggest that these nutraceuticals, when consumed as a part of the diet or as additional supplementation, can potentially negate the cellular level adverse effects of exposure to particulate pollution. The potential benefits of adopting a non-pharmacological diet-based approach to air pollution-induced disease management have also been discussed. We argue that before a nutraceuticals-based approach can be used for widespread public adoption, further research, especially human clinical trials, is essential to confirm the beneficial action of relevant nutraceuticals and to explore the safe limits of human supplementation and the risk of side effects. Future research should focus on systematically translating bench-based knowledge regarding nutraceuticals gained from in vitro and in vivo studies into clinically usable nutritional guidelines.

Medical Foods: Science, Regulation, and Practical Aspects. Summary of a Workshop.

On August 13-14, 2019, the Healthcare Nutrition Council and the ASN held the Medical Foods Workshop: Science, Regulation, and Practical Aspects. Medical food products help patients manage their disease and improve their quality of life. Yet many hurdles exist to getting patients new products. In this workshop, participants addressed some of these hurdles, with specific emphasis on topics like the statutory term distinctive nutritional requirements, the regulatory term modification of the diet alone, the role of clinical guidelines, the requirement that medical foods be used under medical supervision, and differentiation of foods for special dietary use from medical foods, as well as product innovation and future research. Real-world examples were discussed for intractable epilepsy, diabetes, end-stage renal disease, and inflammatory bowel disease.

Positive improvement in palatability of metabolic formula with the use of miraculin protein in patients with inborn errors of metabolism and healthy adults / Cambio positivo en la palatabilidad de la fórmula metabólica con el uso de la proteína miraculina en pacientes con errores innatos del metabolismo y adultos sanos

ABSTRACT As palatability of medical formulas has been documented as unpleasant, new options are required to improve acceptance and adherence in people with inborn errors of metabolism (IEM). Miracle fruit (Synsepalum dulcificum) has a glycoprotein named miraculin that transforms a sour, bitter taste such as the one found in metabolic formula, into a sweet perception. The objective of this work is to analyze the response in the taste perception of metabolic formula with the use of the miraculin tablets in patients with IEM and healthy adults. To test this hypothesis a prospective, longitudinal, quasi-experimental, analytical study was performed. Patients with IEM and healthy adults were recruited. All participants assessed 3 different liquids (lemon, apple cider vinegar and metabolic formula) before and after the administration of miraculin tablets and completed a questionnaire. The sensory responses were evaluated using hedonic scales, analyzed with nonparametric tests for paired data. Seven patients with IEM and 14 healthy subjects were included. After miraculin intake 57% of patients (Z ≤ -1.89 p= 0.059) and healthy adults (Z≤ -2.31 p= 0.021) had a positive change in their taste perception. The absolute frequency of patients who did not like the metabolic formula decreased from 4 to 1, and in patients who liked it or loved, it increased from 0 to 2 and from 0 to 1 respectively; the frequency of patients who perceived the metabolic formula as indifferent or hated it, did not change. Response in taste perception had a positive change of 57% in both groups. The use of miraculin tablets may improve palatability of metabolic formula.

RESUMEN La palatabilidad de las fórmulas médicas se ha reportado como desagradable, se requieren nuevas opciones para mejorar la aceptación en personas con errores innatos del metabolismo (EIM). La fruta milagrosa (Synsepalum dulcificum) contiene una glucoproteína llamada miraculina que transforma el sabor agrio y amargo en dulce. El objetivo fue analizar la respuesta en la percepción del sabor de la fórmula metabólica con el uso de las tabletas de miraculina en pacientes con EIM y adultos sanos. Se realizó un estudio analítico prospectivo, longitudinal, cuasi-experimental. Los participantes evaluaron la percepción de 3 líquidos (limón, vinagre de manzana y fórmula metabólica) antes y después de la administración de tabletas de miraculina y completaron un cuestionario. Las respuestas sensoriales se evaluaron mediante escalas hedónicas, analizadas con pruebas no paramétricas para datos pareados. Se incluyeron 7 pacientes con EIM y 14 adultos sanos. Después de la miraculina el 57% de los pacientes (Z ≤ -1,89 p= 0,059) y adultos sanos (Z≤ -2,31 p= 0,021) tuvieron un cambio positivo en su percepción del sabor. La frecuencia absoluta de pacientes a los que no les gustó la fórmula disminuyó de 4 a 1, y en quienes les gustó o les encantó, aumentó de 0 a 2 y de 0 a 1 respectivamente; la frecuencia de los pacientes que percibieron la fórmula como indiferente u odiada, no cambió. La respuesta en la percepción del sabor cambió positivamente en el 57% en ambos grupos. El uso de miraculina puede mejorar la palatabilidad de la fórmula metabólica.

A tasting experiment comparing food and nutritional supplement in anorexia nervosa.

Anorexia nervosa (AN) is a severe psychiatric disorder leading to life-threatening emaciation. Weight restoration is crucial in treatment but few data are available on how to achieve it. Nutritional supplements are needed in treatment but patients' preferences about natural versus medical foods and their gustatory/hedonic perception are unclear. We aimed to measure disgust and reward-based eating in AN and to assess psychological, interoceptive awareness-related, behavioral, and hedonic aspects comparing natural versus medical food. Thirty-three inpatients with AN and 39 healthy controls (HCs) were recruited and received 50 ml of either apricot juice or nutritional liquid supplement with apricot flavor on two consecutive days. Disgust, reward-based eating, and eating psychopathology were evaluated. Visual Analogue Scales measuring anxiety, hunger, confusion about internal states, need for over-exercise, restraint, and satiety were completed before and after the experiment. Disgust and hedonic responses were measured after the experiment. Patients with AN reported preserved disgust sensitivity and higher reward-based eating drive. When compared to HCs, inpatients with AN reported higher scores on anxiety, hunger, confusion about internal states, urge to over-exercise, urge to eating restraint, and satiety before and after the tasting experiment. The supplement slightly increased patients' anxiety with HCs reporting the same trend. Still, patients reported more food-related disgust after the supplement but their overall hedonic evaluation was similar for both conditions. Also, anxiety, confusion about internal states, and urge to over-exercise and restraint did not significantly increase after consuming either food. Therefore, if we take into account patients' level of heightened satiety and suppressed hunger, supplements could be helpful for patients with severe AN since greater energy intakes could be provided with only small volumes of food and little changes of eating concerns.

Nutrient intake, body composition, and blood phenylalanine control in children with phenylketonuria compared to healthy controls.

BACKGROUND: Phenylketonuria (PKU) treatment consists of life-long protein restriction and Phe-free medical foods for adequate nutritional intake and growth. A relationship between body composition and blood phenylalanine (Phe) concentrations in subjects with PKU has been proposed but this has not been consistently reported. METHODS: Dietary intake, lean body mass (LBM) and fat mass (FM) were measured in 30 pediatric subjects with PKU compared to 30 age, and sex matched controls. The relationship between body composition and blood Phe was analyzed within the PKU cohort from clinically collected dried blood spot Phe concentrations. RESULTS: Male subjects with PKU had less LBM% and more FM% than controls (p = .024). There was no difference in LBM% and FM% among female subjects. Age (p = .02) and FM% (p = .02) were positively correlated to dried blood spot Phe. Synthetic protein intake (g/kg body weight) was negatively correlated with dried blood spot Phe (p = .04). Natural protein intake was not related to blood spot Phe. CONCLUSIONS: Children with PKU face additional dietary challenges maintaining healthy growth and body composition while keeping Phe levels low. We observed higher FM% and lower LBM% in male subjects with PKU. Correlations do not prove cause and effect but suggest a relationship between increased blood Phe, lower synthetic protein intake and increased FM%. Future studies may explore if lower blood Phe concentrations is associated with a lower FM% and higher LBM%; particularly among adult patients now managed on pegvaliase (Palynziq®) who consume normal amounts of natural protein or among younger patients who consume glycomacropeptide (GMP).

Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease.

Flavonoids, one of the most abundant phytochemicals in a diet rich in fruits and vegetables, have been recognized as possessing anti-proliferative, antioxidant, anti-inflammatory, and estrogenic activities. Numerous cellular and animal-based studies show that flavonoids can function as antioxidants by preventing DNA damage and scavenging reactive oxygen radicals, inhibiting formation of DNA adducts, enhancing DNA repair, interfering with chemical damage by induction of Phase II enzymes, and modifying signaling pathways. Recent evidence also shows their ability to regulate the immune system. However, findings from clinical trials have been mixed with no clear consensus on dose, frequency, or type of flavonoids best suited to elicit many of the beneficial effects. Delivery of these bioactive compounds to their biological targets through "targeted designed" food processing strategies is critical to reach effective concentration in vivo. Thus, the identification of novel approaches that optimize flavonoid bioavailability is essential for their successful clinical application. In this review, we discuss the relevance of increasing flavonoid bioavailability, by agricultural engineering and "targeted food design" in the context of the immune system and cancer.

Optimizing foods for special dietary use in Canada: key outcomes and recommendations from a tripartite workshop.

Many health conditions result in unique nutritional requirements (e.g., protein restriction, low energy, fortification) and the need to consume foods in nontraditional formats (e.g., liquid diets, supplements, tube feeding). In Canada, 45% of hospital patients are malnourished upon admission, resulting in prolonged hospital stays, increased health care costs, and higher mortality rates. Fortunately, advances in nutrition and food science enabled the development of products that provide nutritional support for individuals in hospital and at home. In Canada, these products are defined as Foods for Special Dietary Use (FSDUs). Canada's regulation of FSDUs (Division 24 of the Food and Drug Regulations) is particularly stringent and outdated, which results in products that do not meet current nutritional recommendations or allow application of current technologies, and lack harmonization with other countries. Many of these issues also apply to the Infant Food regulations in Canada. To provide vulnerable populations with optimal nutrition, experts have suggested modernization of Canadian FSDU regulations. A multi-stakeholder workshop established several recommendations and goals toward that end while ensuring the safety of consumers. These include (i) assessing other jurisdictions' regulations; (ii) tracking products currently on the market; (iii) temporary marketing authorizations to permit products on the market and collect data; (iv) use of incorporation by reference for compositional requirements; (v) support for research of FSDU and nutritional needs of special population; and (vi) better understanding accessibility to these products. Overall, the proposed vision is for a modern, safe, flexible, innovative, and health-driven regulatory framework for FSDU in Canada.

Review of Worldwide Regulations and Management Systems for Medical Foods

Enteral nutrition (EN) formulas are foods that are used to improve the nutritional status of patients and these foods' safety and quality must be ensured. Therefore, EN formulas in other countries are managed differently from that of general foods. We investigated the direction of development of the relevant laws regulations and guidelines pertaining to EN formulas and we compared these laws regulations and guidelines from different countries, including Korea. The United States and Europe manage EN formulas as foods, but they are managed differently compared to general foods because of separate laws or programs pertaining to EN foods. In addition, the use of the formulas does not necessarily require a prescription, but when used by prescription, then medical insurance covers them. In Japan, there are two types of EN formulas, food and drug, and there are differences for their management and insurance coverage. In the case of Korea, EN formulas are classified as food and drug, and different management and insurance are applied in each case, which inhibits their systematic management and industrial development. Integration of a management system and establishment of a legal foundation is necessary for the systematic management and development of EN formula in Korea.

Sex differences in body composition and bone mineral density in phenylketonuria: A cross-sectional study.

BACKGROUND: Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). OBJECTIVE: To determine if there are differences in BMD and body composition between male and female participants with PKU. METHODS: From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each. RESULTS: Male participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. CONCLUSIONS: Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.

Recent advances of medical foods in China: The opportunities and challenges under standardization.

Malnutrition with high incidence in hospitalized patients in China has brought a significant burden of disease. Although many clinical studies have demonstrated the importance of nutritional for patients with malnutrition, the application of medical foods in China is still restricted. For the classification, limits, production and registration of medical foods, the Chinese government newly enacted a series of regulations. In this review, comparing the policy, researches, and product variety of medical foods in China with other countries, although the current status of the development of medical foods in China is still far behind that of developed countries, some of regulations are stricter than those of many other countries or organizations. The medical foods in China are divided into four categories, the nutrients and environmental contaminants are limited to ensure the safety. As a prospect, the development of medical foods in China is expected to get out of the predicament of lack of emphasis, shortage of supply, backward of local processing technology and the imperfect management system. After all, in view of the huge population and the increasing demand of nutrition in China, there must be a very good prospect for the future development of the medical foods industry in China.

Medicinal Foods for Functional GI Disorders.

PURPOSE OF REVIEW: Over the past 10 years, there has been a dramatic increase in basic and clinical research involving functional gastrointestinal disorders (FGIDs). New diagnostic and biomarker procedures are helping to identify physiologic disruptions associated with FGIDs on cellular and molecular levels. Simultaneously, clinicians are using new approaches to help manage patients with FGIDs. Among these, an important component of care has been the use of medical foods. These include probiotics, prebiotics, synbiotics, peppermint oil, caraway oil, curcumin, bovine immunoglobulin and many others. RECENT FINDINGS: The putative effects of different medical foods make these therapies attractive for the management of FGIDs. These include effects on several pathophysiological mechanisms such as anti-inflammatory, smooth muscle relaxation, analgesia, mitigation of gut barrier dysfunction, and stimulation or inhibition of gastrointestinal receptors. Recent research has also demonstrated the efficacy of medical food products such as peppermint oil and serum-derived bovine immunoglobulin for the management of irritable bowel syndrome. Older data supports the probiotic VSL#3 and Bifidobacterium species. For functional dyspepsia, positive effects have been observed with the combination of caraway seed oil and peppermint oil as well as with STW-5, a botanical combination preparation, although robust RCTs are lacking. With advancing knowledge regarding the pathogenesis of FGIDs, it is likely that the compounds available in the medical food category will increase dramatically, and they could play an important role in the management of several common and bothersome gastrointestinal conditions in the future.

Protein intake and physical activity are associated with body composition in individuals with phenylalanine hydroxylase deficiency.

OBJECTIVE: Determine whether body composition as it relates to dietary protein in patients with phenylalanine hydroxylase (PAH) deficiency is associated with genotype, dietary factors, and lifestyle choices. METHODS: We examined associations between protein intake (intact and medical foods: MF) and body composition in PAH-deficient patients along with, physical activity, and genotype. Protein intakes (total, intact, and MF) were analysed from three-day food records with Nutrition Data System for Research (NDSR) in 59 children and 27 adults (N=86, median age=16.0years). The severity of PAH deficiency was classified using the genotype assigned value method (AV sum). Physical activity was assessed using a study-developed question (light vs. intense activity). Body composition was measured by DXA, including android:gynoid ratio (A:G), fat-free mass index (FFMI), fat mass index (FMI), and FMI:FFMI ratio. RESULTS: High intact protein intake was associated with high FFMI (rs=0.75, p=0.008) and low FMI:FFMI (rs=-0.59, p=0.04) in adults. Only in children, MF protein (rs=0.38, p=0.04) was directly proportional to FFMI. Median intact protein intakes of adults (25.1 vs. 9.9g/d, p<0.001) and children (11 vs. 6g/d, p<0.001) were higher than prescribed. Only in adults, the actual median MF protein intake was lower than prescribed (53 vs. 60g/d, p=0.03). In adults and children, light activity was associated with higher fat mass indices compared to intense activity (adults: FMI:FFMI: ß=1.1, p=0.001, children: FMI:FFMI: ß=1.1, p=0.007; FMI ß=2.1, p=0.01; A:G ß=1.1, p=0.04). All associations remained significant after covariate adjustment. Genotype was not associated with body composition. CONCLUSIONS: Although fat-free mass in adults was positively associated with intact protein intake, it should be consumed as prescribed per individual tolerance to maintain plasma Phe concentrations within treatment range. In children, total protein maximized with MF should be encouraged to promote lean mass. Nutrition counselling could be complemented with physical activity recommendations for optimal clinical outcomes.

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders.

In addition to drugs approved by the US Food and Drug Administration (FDA) that treat, cure, or mitigate disease, medical foods are a tool to help manage chronic conditions and diseases. A medical food, according to the FDA, is a food that is developed to be eaten or administered enterally under the guidance of a physician and that is meant for the specific dietary management of a condition or disease for which distinctive nutritional requirements, based upon known scientific principles, are established by medical evaluation. A variety of medical foods exist to help manage a wide range of medical conditions, from Alzheimer disease to HIV-associated enteropathy. EnteraGam contains serum-derived bovine immunoglobulin/protein isolate, which has been studied extensively in diarrhea-predominant irritable bowel syndrome, inflammatory bowel disease (IBD), and HIV-associated enteropathy. VSL#3 is a probiotic that is used in pouchitis for patients with ulcerative colitis as well as irritable bowel syndrome. Modulen IBD is a whole-protein, sole-nutrition formulation used to manage the active phase of Crohn's disease. Vivonex is an elemental diet that is used in a variety of diseases associated with severe gastrointestinal dysfunction. Medical foods are safe and must have proven efficacy in helping to manage a variety of gastrointestinal conditions and diseases. These therapies represent tools that can be used prior or in addition to traditional medical therapies. This article discusses the history and development of medical foods under the FDA and concentrates specifically on medical foods used to help manage diseases of the gastrointestinal tract.

Nutritional interventions in primary mitochondrial disorders: Developing an evidence base.

In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD.

Normal vitamin D levels and bone mineral density among children with inborn errors of metabolism consuming medical food-based diets.

A higher incidence of osteopenia is observed among children with inherited metabolic disorders (inborn errors of metabolism, or IEMs) who consume medical food-based diets that restrict natural vitamin D-containing food sources. We evaluated the vitamin D status of children with IEMs who live in the Pacific Northwest with limited sun exposure and determined whether bone mineral density (BMD) in children with phenylketonuria (PKU), the most common IEM, correlated with diet or biochemical markers of bone metabolism. We hypothesized that children with IEMs would have lower serum vitamin D concentrations than controls and that some children with PKU would have reduced bone mineralization. A retrospective record review of 88 patients with IEMs, and 445 children on unrestricted diets (controls) found the 25-hydroxyvitamin D concentrations were normal and not significantly different between groups (IEM patients, 27.1 ± 10.9; controls, 27.6 ± 11.2). Normal BMD at the hip or spine (-2

The Nutraceutical Bioavailability Classification Scheme: Classifying Nutraceuticals According to Factors Limiting their Oral Bioavailability.

The oral bioavailability of a health-promoting dietary component (nutraceutical) may be limited by various physicochemical and physiological phenomena: liberation from food matrices, solubility in gastrointestinal fluids, interaction with gastrointestinal components, chemical degradation or metabolism, and epithelium cell permeability. Nutraceutical bioavailability can therefore be improved by designing food matrices that control their bioaccessibility (B*), absorption (A*), and transformation (T*) within the gastrointestinal tract (GIT). This article reviews the major factors influencing the gastrointestinal fate of nutraceuticals, and then uses this information to develop a new scheme to classify the major factors limiting nutraceutical bioavailability: the nutraceutical bioavailability classification scheme (NuBACS). This new scheme is analogous to the biopharmaceutical classification scheme (BCS) used by the pharmaceutical industry to classify drug bioavailability, but it contains additional factors important for understanding nutraceutical bioavailability in foods. The article also highlights potential strategies for increasing the oral bioavailability of nutraceuticals based on their NuBACS designation (B*A*T*).

Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning.

Inborn errors of metabolism (IEM) are genetic disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. In the U.S., many IEM are detected through state newborn screening (NBS) programs. To inform research on IEM and provide necessary resources for researchers, we are providing: tabulation of ten-year state NBS data for selected IEM detected through NBS; costs of medical foods used in the management of IEM; and an assessment of corporate policies regarding provision of nutritional interventions at no or reduced cost to individuals with IEM. The calculated IEM incidences are based on analyses of ten-year data (2001-2011) from the National Newborn Screening Information System (NNSIS). Costs to feed an average person with an IEM were approximated by determining costs to feed an individual with an IEM, minus the annual expenditure for food for an individual without an IEM. Both the incidence and costs of nutritional intervention data will be useful in future research concerning the impact of IEM disorders on families, individuals and society.